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©The Author(s) 2023.
World J Gastroenterol. Apr 28, 2023; 29(16): 2479-2494
Published online Apr 28, 2023. doi: 10.3748/wjg.v29.i16.2479
Published online Apr 28, 2023. doi: 10.3748/wjg.v29.i16.2479
Table 1 Distribution of baseline characteristics in 634 chronic hepatitis B patients with alanine transaminase < upper limit of normal
Parameters | All patients (n = 634) | HBV DNA levels (EASL guidelines) | HBV DNA levels (CMA guidelines) | ||||||
Low/moderate replication (n = 336) | High replication (n = 298) | χ2/t /Z/u | P value | Low/moderate replication (n = 377) | High replication (n = 257) | χ2/t/Z/u | P value | ||
Age, mean ± SD, yr | 35.61 ± 10.30 | 38.09 ± 9.99 | 32.82 ± 9.95 | 6.640 | < 0.001 | 37.34 ± 10.17 | 33.07 ± 9.99 | 5.222 | < 0.001 |
Male, n (%) | 349 (55.05) | 192 (57.14) | 157 (52.68) | 1.269 | 0.260 | 209 (55.44) | 140 (54.47) | 0.057 | 0.811 |
HBeAg positive, n (%) | 432 (68.14) | 142 (42.26) | 290 (97.31) | 220.486 | < 0.001 | 180 (47.74) | 252 (98.05) | 178.165 | < 0.001 |
ALB, mean ± SD, g/L | 42.72 ± 4.45 | 42.91 ± 4.97 | 42.49 ± 3.78 | 1.189 | 0.235 | 42.75 ± 4.88 | 42.67 ± 3.74 | 0.220 | 0.826 |
GLB, mean ± SD, g/L | 27.82 ± 4.20 | 27.96 ± 4.11 | 27.66 ± 4.30 | 0.893 | 0.372 | 28.11 ± 4.19 | 27.40 ± 4.18 | 2.105 | 0.036 |
AGR, mean ± SD | 1.57 ± 0.29 | 1.57 ± 0.30 | 1.57 ± 0.28 | -0.148 | 0.882 | 1.56 ± 0.30 | 1.59 ± 0.28 | -1.581 | 0.114 |
ALT, mean ± SD, U/L | 23.77 ± 8.58 | 24.84 ± 8.66 | 22.56 ± 8.34 | 3.372 | 0.001 | 24.38 ± 8.69 | 22.87 ± 8.35 | 2.186 | 0.029 |
AST, mean ± SD, U/L | 24.15 ± 8.91 | 25.00 ± 7.52 | 23.20 ± 10.18 | 2.558 | 0.011 | 25.04 ± 10.28 | 22.85 ± 6.17 | 3.069 | 0.002 |
ALP, mean ± SD, U/L | 71.26 ± 26.06 | 71.52 ± 24.85 | 70.96 ± 27.39 | 0.269 | 0.788 | 71.21 ± 24.99 | 71.32 ± 27.60 | -0.054 | 0.957 |
GGT, median (Q1-Q3), U/L | 18.00 (13.00-25.00) | 20.00 (15.00-30.00) | 16.00 (13.00-23.00) | 4.966 | < 0.001 | 19.00 (14.00-29.00) | 16.00 (13.00-23.00) | 4.069 | < 0.001 |
WBC count, mean ± SD, | 5.39 ± 1.42 | 5.33 ± 1.39 | 5.47 ± 1.45 | -1.208 | 0.228 | 5.33 ± 1.44 | 5.48 ± 1.39 | -1.321 | 0.187 |
NLR, mean ± SD | 2.03 ± 1.24 | 2.05 ± 1.37 | 2.01 ± 1.08 | 0.443 | 0.658 | 2.04 ± 1.33 | 2.01 ± 1.09 | 0.298 | 0.766 |
PLT count, mean ± SD, | 175.67 ± 48.83 | 163.93 ± 47.39 | 188.90 ± 47.09 | -6.641 | < 0.001 | 166.86 ± 47.55 | 188.58 ± 47.90 | -5.629 | < 0.001 |
HBV DNA, mean ± SD, log IU/mL | 6.18 ± 1.87 | 4.68 ± 1.26 | 7.88 ± 0.50 | -41.111 | < 0.001 | 4.95 ± 1.41 | 7.99 ± 0.44 | -33.427 | < 0.001 |
APRI, median (Q1–Q3) | 0.33 (0.25-0.44) | 0.36 (0.28-0.51) | 0.29 (0.23-0.38) | 6.936 | < 0.001 | 0.36 (0.27-0.48) | 0.30 (0.23-0.38) | 5.725 | < 0.001 |
FIB-4, median (Q1-Q3) | 0.99 (0.69-1.38) | 1.13 (0.83-1.61) | 0.80 (0.58-1.13) | 8.109 | < 0.001 | 1.09 (0.79-1.56) | 0.81 (0.59-1.13) | 6.877 | < 0.001 |
LIF-5, mean ± SD | 0.40 ± 0.15 | 0.45 ± 0.15 | 0.36 ± 0.14 | 7.832 | < 0.001 | 0.44 ± 0.15 | 0.35 ± 0.14 | 7.195 | < 0.001 |
Liver inflammatory activity | |||||||||
A0, n (%) | 117 (18.45) | 58 (17.26) | 59 (19.80) | 4.189 | < 0.001 | 61 (16.18) | 56 (21.79) | 4.426 | < 0.001 |
A1, n (%) | 381 (60.10) | 174 (51.79) | 207 (69.46) | 206 (54.64) | 175 (68.09) | ||||
A2, n (%) | 97 (15.30) | 73 (21.73) | 24 (8.05) | 78 (20.69) | 19 (7.39) | ||||
A3, n (%) | 39 (6.15) | 31 (9.23) | 8 (2.68) | 32 (8.49) | 7 (2.72) | ||||
≥ A2, n (%) | 136 (21.45) | 104 (30.95) | 32 (10.74) | 38.299 | < 0.001 | 110 (29.18) | 26 (10.12) | 32.952 | < 0.001 |
Liver fibrosis | |||||||||
F0, n (%) | 148 (23.34) | 61 (18.15) | 87 (29.19) | 6.382 | < 0.001 | 70 (18.57) | 78 (30.35) | 6.053 | < 0.001 |
F1, n (%) | 332 (52.37) | 153 (45.54) | 179 (60.07) | 179 (47.48) | 153 (59.53) | ||||
F2, n (%) | 87 (13.72) | 65 (19.35) | 22 (7.38) | 70 (18.57) | 17 (6.61) | ||||
F3, n (%) | 37 (5.84) | 29 (8.63) | 8 (2.68) | 30 (7.96) | 7 (2.72) | ||||
F4, n (%) | 30 (4.73) | 28 (8.33) | 2 (0.67) | 28 (7.43) | 2 (0.78) | ||||
≥ F2, n (%) | 154 (24.29) | 122 (36.31) | 32 (10.74) | 56.155 | < 0.001 | 128 (33.95) | 26 (10.12) | 47.212 | < 0.001 |
Treatment indication | |||||||||
< A2 and < F2, n (%) | 442 (69.72) | 191 (56.85) | 251 (84.23) | 56.089 | < 0.001 | 224 (59.42) | 218 (84.82) | 46.730 | < 0.001 |
≥ A2 or/and ≥ F2, n (%) | 192 (30.28) | 145 (43.15) | 47 (15.77) | 153 (40.58) | 39 (15.18) |
Table 2 Comparison of parameters among patients with alanine transaminase < upper limit of normal and different pathological states (Entire cohort)
Parameters | Liver inflammatory activity | Liver fibrosis | Treatment indication | P value | |||
< A2 (n = 498) | ≥ A2 (n = 136) | < F2 (n = 480) | ≥ F2 (n = 154) | < A2 and < F2 (n = 442) | ≥ A2 or/and ≥ F2 (n = 192) | ||
Age, mean ± SD, yr | 34.68 ± 9.88 | 39.02 ± 11.10 | 34.36 ± 9.86 | 39.52 ± 10.71 | 34.28 ± 9.84 | 38.69 ± 10.70 | < 0.001, < 0.001, < 0.001 |
Male, n (%) | 268 (53.82) | 81 (59.56) | 253 (52.71) | 96 (62.34) | 234 (52.94) | 115 (59.90) | 0.232, 0.037, 0.105 |
HBeAg positive, n (%) | 354 (71.08) | 78 (57.35) | 350 (72.92) | 82 (53.25) | 323 (73.08) | 109 (56.77) | 0.002, < 0.001, < 0.001 |
ALB, mean ± SD, g/L | 43.06 ± 3.96 | 41.45 ± 5.75 | 42.96 ± 4.32 | 41.95 ± 4.75 | 43.06 ± 4.01 | 41.92 ± 5.24 | < 0.001, 0.014, 0.003 |
GLB, mean ± SD, g/L | 27.46 ± 4.09 | 29.14 ± 4.35 | 27.54 ± 4.06 | 28.70 ± 4.51 | 27.49 ± 4.08 | 28.57 ± 4.38 | < 0.001, 0.003, 0.003 |
AGR, mean ± SD | 1.60 ± 0.27 | 1.46 ± 0.33 | 1.59 ± 0.28 | 1.50 ± 0.31 | 1.60 ± 0.27 | 1.50 ± 0.32 | < 0.001, 0.001, < 0.001 |
ALT, mean ± SD, U/L | 22.81 ± 8.48 | 27.26 ± 8.07 | 22.80 ± 8.48 | 26.80 ± 8.20 | 22.45 ± 8.43 | 26.80 ± 8.16 | < 0.001, < 0.001, < 0.001 |
AST, mean ± SD, U/L | 22.93 ± 6.24 | 28.62 ± 14.26 | 22.79 ± 6.41 | 28.41 ± 13.26 | 22.64 ± 6.26 | 27.63 ± 12.45 | < 0.001, < 0.001, < 0.001 |
ALP, mean ± SD, U/L | 68.68 ± 24.45 | 80.67 ± 29.48 | 68.62 ± 23.35 | 79.49 ± 31.80 | 68.58 ± 23.86 | 77.41 ± 29.68 | < 0.001, < 0.001, < 0.001 |
GGT, mean ± SD, U/L | 20.24 ± 13.58 | 34.91 ± 33.78 | 19.87 ± 13.63 | 34.34 ± 31.87 | 19.91 ± 13.78 | 31.38 ± 29.60 | < 0.001, < 0.001, < 0.001 |
WBC count, mean ± SD, × 109/L | 5.40 ± 1.41 | 5.33 ± 1.53 | 5.43 ± 1.44 | 5.26 ± 1.40 | 5.41 ± 1.42 | 5.33 ± 1.46 | 0.622, 0.210, 0.491 |
NLR, mean ± SD | 2.05 ± 1.21 | 1.96 ± 1.35 | 2.07 ± 1.31 | 1.91 ± 0.99 | 2.04 ± 1.21 | 2.02 ± 1.32 | 0.447, 0.158, 0.824 |
PLT count, mean ± SD, × 109/L | 184.72 ± 44.67 | 142.52 ± 49.26 | 186.16 ± 44.28 | 142.94 ± 47.99 | 187.73 ± 43.49 | 147.90 ± 49.24 | < 0.001, < 0.001, < 0.001 |
HBV DNA, mean ± SD, log IU/mL | 6.35 ± 1.91 | 5.56 ± 1.59 | 6.44 ± 1.87 | 5.39 ± 1.64 | 6.47 ± 1.88 | 5.52 ± 1.67 | < 0.001, < 0.001, < 0.001 |
APRI, mean ± SD | 0.33 ± 0.14 | 0.59 ± 0.42 | 0.32 ± 0.13 | 0.58 ± 0.39 | 0.32 ± 0.12 | 0.54 ± 0.37 | < 0.001, < 0.001, < 0.001 |
FIB-4, mean ± SD | 1.01 0.53 | 1.81 ± 1.34 | 0.97 ± 0.49 | 1.81 ± 1.28 | 0.96 ± 0.49 | 1.67 ± 1.21 | < 0.001, < 0.001, < 0.001 |
LIF-5, mean ± SD | 0.37 ± 0.13 | 0.54 ± 0.17 | 0.36 ± 0.12 | 0.53 ± 0.16 | 0.36 ± 0.12 | 0.51 ± 0.16 | < 0.001, < 0.001, < 0.001 |
Table 3 Predictors of significant liver histology in 634 patients with chronic hepatitis B and alanine transaminase < upper limit of normal detected using a step-forward binary logistic regression model
Variables | Regression coefficient | Standard error | Wald’s value | P value | OR | OR 95%CI | ||
Upper limit | Lower limit | |||||||
< A2 vs ≥ A2 | Age | -0.039 | 0.014 | 7.853 | 0.005 | 0.962 | 0.936 | 0.988 |
GGT | 0.015 | 0.006 | 5.970 | 0.015 | 1.015 | 1.003 | 1.027 | |
HBV DNA | -0.147 | 0.064 | 5.306 | 0.021 | 0.863 | 0.761 | 0.978 | |
LIF-5 | 9.616 | 1.152 | 69.727 | 0.000 | 15002.994 | 1570.174 | 143353.477 | |
Constant | -3.643 | 0.685 | 28.240 | 0.000 | 0.026 | |||
Eliminate diagnostic models | HBV DNA | -0.161 | 0.063 | 6.429 | 0.011 | 0.851 | 0.752 | 0.964 |
< F2 vs ≥ F2 | GGT | 0.016 | 0.006 | 5.968 | 0.015 | 1.016 | 1.003 | 1.029 |
HBV DNA | -0.229 | 0.061 | 14.251 | 0.000 | 0.796 | 0.707 | 0.896 | |
APRI | 2.747 | 0.921 | 8.890 | 0.003 | 15.593 | 2.563 | 94.859 | |
LIF-5 | 4.759 | 1.285 | 13.708 | 0.000 | 116.591 | 9.390 | 1447.723 | |
Constant | -3.392 | 0.577 | 34.608 | 0.000 | 0.034 | |||
Eliminate diagnostic models | HBV DNA | -0.247 | 0.061 | 16.523 | 0.000 | 0.781 | 0.693 | 0.880 |
< A2 and < F2 vs ≥ A2 or/and ≥ F2 | HBV DNA | -0.199 | 0.055 | 13.233 | 0.000 | 0.820 | 0.737 | 0.913 |
APRI | 3.124 | 0.888 | 12.393 | 0.000 | 22.747 | 3.995 | 129.530 | |
LIF-5 | 4.733 | 1.182 | 16.038 | 0.000 | 113.618 | 11.207 | 1151.897 | |
Constant | -2.903 | 0.522 | 30.931 | 0.000 | 0.055 | |||
Eliminate diagnostic models | HBV DNA | -0.221 | 0.056 | 15.782 | 0.000 | 0.801 | 0.718 | 0.894 |
Table 4 Predictors of significant liver histology in propensity score-matched pairs
Variables | EASL guidelines (316 pairs) | CMA guidelines (277 pairs) | ||||||
≥ A2 or/and ≥ F2 | < A2 and < F2 | χ2/t/Z | SMD | ≥ A2 or/and ≥ F2 | < A2 and < F2 | χ2/t/Z | SMD | |
Male, n (%) | 171 (54.11) | 168 (53.16) | 0.057 | 0.811 | 138 (49.82) | 153 (55.23) | 1.629 | 0.202 |
HBeAg positive, n (%) | 305 (96.52) | 306 (96.84) | 0.049 | 0.824 | 271 (97.83) | 271 (97.83) | 0 | 1.000 |
Age, mean ± SD, yr | 32.92 ± 10.13 | 33.06 ± 9.96 | -0.178 | 0.859 | 32.54 ± 9.04 | 33.31 ± 10.07 | -0.937 | 0.349 |
ALB, mean ± SD, g/L | 42.30 ± 4.59 | 42.65 ± 3.78 | -1.046 | 0.296 | 42.35 ± 4.81 | 42.79 ± 3.76 | -1.187 | 0.236 |
GLB, mean ± SD, g/L | 27.74 ± 4.83 | 27.74 ± 4.26 | 0.019 | 0.985 | 27.23 ± 4.56 | 27.53 ± 4.25 | -0.809 | 0.419 |
AGR, mean ± SD | 1.57 ± 0.33 | 1.57 ± 0.28 | -0.037 | 0.971 | 1.59 ± 0.29 | 1.59 ± 0.28 | 0.198 | 0.843 |
ALT, mean ± SD, U/L | 23.81 ± 8.29 | 22.78 ± 8.29 | 1.569 | 0.117 | 23.18 ± 9.10 | 23.00 ± 8.38 | 0.235 | 0.814 |
AST, mean ± SD, U/L | 22.13 ± 8.55 | 22.57 ± 5.76 | -0.769 | 0.442 | 21.87 ± 7.74 | 22.72 ± 5.70 | -1.465 | 0.143 |
ALP, mean ± SD, U/L | 71.64 ± 27.61 | 70.56 ± 27.09 | 0.495 | 0.621 | 72.15 ± 25.92 | 71.37 ± 27.39 | 0.345 | 0.730 |
GGT, median (Q1-Q3), U/L | 16.00 (13.00–23.00) | 16.00 (13.00–23.00) | 0.780 | 0.435 | 16.00 (13.00-24.00) | 17.00 (13.00-23.00) | 0.590 | 0.555 |
WBC count, mean ± SD, | 5.44 ± 1.27 | 5.47 ± 1.38 | -0.276 | 0.783 | 5.51 ± 1.31 | 5.48 ± 1.30 | 0.274 | 0.784 |
NLR, mean ± SD | 1.91 ± 0.80 | 2.01 ± 1.04 | -1.431 | 0.153 | 1.89 ± 1.01 | 2.00 ± 1.04 | -1.334 | 0.183 |
PLT count, mean ± SD, | 183.43 ± 42.01 | 187.96 ± 47.38 | -1.272 | 0.204 | 184.38 ± 49.39 | 187.11 ± 48.08 | -0.659 | 0.510 |
HBV DNA, mean ± SD, log IU/mL | 5.81 ± 1.23 | 7.90 ± 0.49 | -27.967 | < 0.001 | 5.78 ± 1.42 | 8.01 ± 0.43 | -24.922 | < 0.001 |
APRI, median (Q1– Q3) | 0.31 (0.23-0.38) | 0.29 (0.23-0.38) | 0.507 | 0.612 | 0.32 (0.22–0.39) | 0.30 (0.23-0.38) | -0.147 | 0.883 |
FIB-4, median (Q1–Q3) | 0.80 (0.49-1.11) | 0.80 (0.58-1.12) | 1.460 | 0.144 | 0.74 (0.50-1.17) | 0.82 (0.59-1.13) | -1.110 | 0.267 |
LIF-5, mean ± SD | 0.37 ± 0.14 | 0.36 ± 0.14 | 0.903 | 0.367 | 0.35 ± 0.14 | 0.36± 0.14 | -0.187 | 0.852 |
- Citation: Jiang SW, Lian X, Hu AR, Lu JL, He ZY, Shi XJ, Zhu DD, Wang ZY, Huang GC. Liver histopathological lesions is severe in patients with normal alanine transaminase and low to moderate hepatitis B virus DNA replication. World J Gastroenterol 2023; 29(16): 2479-2494
- URL: https://www.wjgnet.com/1007-9327/full/v29/i16/2479.htm
- DOI: https://dx.doi.org/10.3748/wjg.v29.i16.2479