The Influence of Histologic Inflammation on the Improvement of Liver Stiffness Values Over 1 and 3 Years
Abstract
:1. Introduction
2. Methods
2.1. Patients and Study Protocol
2.2. Liver Biopsy and Histology
2.3. Transient Elastography
2.4. Statistical Analysis
3. Results
3.1. Baseline Characteristics
3.2. Related Factors Determining Baseline LS Value
3.3. Factors Associated with Improvement of LS Value
3.4. Paired Liver Biopsy with Paired LSM
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Baseline (n = 678) | 1-year (n = 358) | 3-year (n = 244) |
---|---|---|---|
Age, year, mean (SD) | 47.12 (12.25) | 48.54 (11.84) | 49.57 (10.42) |
Sex, n (%) | |||
Male | 329 (48.5) | 181 (50.6) | 120 (49.2) |
Female | 349 (51.5) | 177 (49.4) | 124 (50.8) |
Etiology, n (%) | |||
HBV | 419 (61.8) | 242 (67.6) | 173 (70.9) |
HCV | 183 (27.0) | 70 (19.6) | 49 (20.1) |
Alcoholic | 12 (1.8) | 7 (2.0) | 5 (2.0) |
Autoimmune | 32 (4.7) | 21 (5.9) | 8 (3.3) |
NAFLD | 21 (3.1) | 12 (3.4) | 7 (2.9) |
Others | 11 (1.6) | 6 (1.7) | 2 (0.8) |
BMI, kg/m2, mean (SD) | 23.97 (3.44) | NA | NA |
Laboratory findings | |||
AST, U/L, mean (IQR) | 44.0 (30.0–77.0) | 37.0 (22.0–38.0) | 28.0 (17.0–30.0) |
ALT, U/L, mean (IQR) | 46.0 (29.0–83.0) | 39.0 (26.0–39.0) | 30.0 (17.0–30.0) |
Total bilirubin, mg/dL, mean (SD) | 1.11 (1.41) | 0.82 (0.46) | 1.02 (0.92) |
Albumin, mg/dL, mean (SD) | 4.15 (0.53) | 4.35 (0.34) | 4.34 (0.34) |
Prothrombin time, INR, mean (SD) | 1.01 (0.46) | 0.97 (0.14) | 0.89 (0.27) |
LSM value, kPa, mean (IQR) | 10.5 (7.3–19.6) | 8.4 (5.3–12.0) | 7.0 (1.8–10.0) |
Liver biopsy, n (%) | |||
Fibrosis | |||
F0 | 13 (1.9) | ||
F1 | 96 (14.2) | ||
F2 | 132 (19.5) | ||
F3 | 186 (27.4) | ||
F4 | 251 (37.0) | ||
Steatosis | |||
No steatosis | 370 (64.2) | ||
Mild | 156 (27.1) | ||
Moderate | 36 (6.3) | ||
Severe | 14 (2.4) | ||
Inflammation | |||
No inflammation | 28 (4.1) | ||
Mild | 278 (41.0) | ||
Moderate | 279 (41.2) | ||
Severe | 93 (13.7) |
Variable | Univariable | Multivariable | ||
---|---|---|---|---|
β (95% CI) | p Value | β (95% CI) | p Value | |
Age, year | 0.175 (0.091 to 0.258) | <0.001 | ||
Sex, male | 0.158 (−1.857 to 2.174) | 0.877 | ||
Viral etiology | −5.530 (−8.487 to −2.573) | <0.001 | −3.560 (−5.994 to −1.125) | 0.004 |
BMI, kg/m2 | 0.115 (−0.223 to 0.452) | 0.505 | ||
Laboratory findings | ||||
Platelet, 109/L | −0.073 (−0.088 to −0.058) | <0.001 | −0.024 (−0.039 to −0.010) | 0001 |
AST, U/L | 0.011 (0.005 to 0.016) | 0.001 | ||
ALT, U/L | 0.005 (0.000 to 0.009) | 0.032 | ||
Total bilirubin, mg/mL | 2.781 (2.153 to 3.409) | <0.001 | 1.904 (1.408 to 2.400) | <0.001 |
Albumin, mg/dL | −12.387 (−14.033 to −10.741) | <0.001 | −5.120 (−6.862 to −3.378) | <0.001 |
Prothrombin time, INR | 8.789 (6.859 to 10.719) | <0.001 | 4.913 (3.411 to 6.415) | <0.001 |
Creatinine, mg/dL | −0.706 (−1.775 to 0.363) | 0.195 | ||
Sodium, mEq/L | −1.428 (−1.809 to −1.047) | <0.001 | −0.494 (−0.789 to −0.198) | 0.001 |
Liver biopsy | ||||
Fibrosis | ||||
F0 | 1 (reference) | 1 (reference) | ||
F1 | −5.570 (−12.045 to 0.906) | 0.092 | −0.341 (−5.928 to 5.246) | 0.905 |
F2 | −3.765 (−10.153 to 2.622) | 0.247 | −1.240 (−6.819 to 4.340) | 0.663 |
F3 | 1.072 (−5.176 to 7.319) | 0.736 | 1.048 (−4.544 to 6.641) | 0.713 |
F4 | 10.277 (4.048 to 16.506) | 0.001 | 8.306 (2.730 to 13.882) | 0.004 |
Steatosis | ||||
No steatosis | 1 (reference) | |||
Mild | 0.868 (−1.562 to 3.299) | 0.483 | ||
Moderate | 1.247 (−2.960 to 5.455) | 0.561 | ||
Severe | 1.339 (−5.092 to 7.770) | 0.683 | ||
Inflammation | ||||
No inflammation | 1 (reference) | 1 (reference) | ||
Mild | 3.897 (−1.265 to 9.058) | 0.139 | 2.347 (−1.487 to 6.182) | 0.230 |
Moderate | 7.414 (2.289 to 12.538) | 0.005 | 3.374 (−0.489 to 7.237) | 0.087 |
Severe | 11.492 (5.977 to 17.007) | <0.001 | 6.476 (2.236 to 10.716) | 0.003 |
Variable | Univariable | Multivariable | ||
---|---|---|---|---|
β (95% CI) | p Value | β (95% CI) | p Value | |
Age, year | −0.028 (−0.115, 0.060) | 0.535 | ||
Sex, male | 0.263 (−1.785, 2.311) | 0.801 | ||
Viral etiology | 3.527 (0.489, 6.566) | 0.023 | ||
BMI, kg/m2 | 0.086 (−0.274, 0.446) | 0.638 | ||
Laboratory findings | ||||
Platelet, 109/L | 0.025 (0.008, 0.043) | 0.005 | 0.027 (0.011, 0.042) | 0.001 |
AST, U/L | −0.012 (−0.018, −0.007) | <0.001 | ||
ALT, U/L | −0.011 (−0.017, −0.005) | <0.001 | ||
Total bilirubin, mg/mL | −1.830 (−2.606, −1.055) | <0.001 | −1.716 (−2.420, −1.011) | <0.001 |
Albumin, mg/dL | 5.882 (3.793, 7.971) | <0.001 | ||
Prothrombin time, INR | −5.399 (−6.994, −3.803) | <0.001 | −4.647 (−6.126, −3.167) | <0.001 |
Creatinine, mg/dL | 3.825 (−1.620, 9.271) | 0.168 | ||
Sodium, mEq/L | 0.438 (0.051, 0.825) | 0.027 | ||
Liver biopsy | ||||
Fibrosis | ||||
F0 | 1 (reference) | |||
F1 | 3.909 (−4.872, 12.691) | 0.382 | ||
F2 | 1.493 (−6.893, 9.880) | 0.726 | ||
F3 | −0.692 (−8.670, 7.285) | 0.865 | ||
F4 | −2.352 (−10.337, 5.633) | 0.563 | ||
Steatosis | ||||
No steatosis | 1 (reference) | |||
Mild | −0.855 (−3.287, 1.576) | 0.489 | ||
Moderate | 0.123 (−3.929, 4.174) | 0.952 | ||
Severe | −3.166 (−8.953, 2.620) | 0.282 | ||
Inflammation | ||||
No inflammation | 1 (reference) | 1 (reference) | ||
Mild | −1.312 (−9.011, 6.387) | 0.738 | −1.256 (−8.298, 5.786) | 0.726 |
Moderate | −3.925 (−11.578, 3.727) | 0.314 | −3.196 (−10.201, 3.808) | 0.370 |
Severe | −9.875 (−17.673, −2.078) | 0.013 | −8.581 (−15.715, −1.447) | 0.019 |
Variable | Univariable | Multivariable | ||
---|---|---|---|---|
β (95% CI) | p Value | β (95% CI) | p Value | |
Age, year | −0.013 (−0.137, 0.11) | 0.832 | ||
Sex, male | −2.451 (−5.004, 0.102) | 0.060 | ||
Viral etiology | −2.200 (−6.681, 2.281) | 0.334 | ||
BMI, kg/m2 | 0.042 (−0.372, 0.456) | 0.842 | ||
Laboratory findings | ||||
Platelet, 109/L | 0.028 (0.005, 0.052) | 0.020 | ||
AST, U/L | −0.013 (−0.022, −0.005) | 0.003 | ||
ALT, U/L | −0.005 (−0.010, 0.001) | 0.091 | ||
Total bilirubin, mg/mL | −1.638 (−2.745, −0.531) | 0.004 | −1.129 (−2.153, −0.105) | 0.031 |
Albumin, mg/dL | 7.138 (4.336, 9.940) | <0.001 | 4.135 (1.187, 7.084) | 0.006 |
Prothrombin time, INR | −7.089 (−10.301, −3.876) | <0.001 | −5.954 (−8.978, −2.931) | <0.001 |
Creatinine, mg/dL | 1.223 (−6.467, 8.912) | 0.754 | ||
Sodium, mEq/L | 0.429 (−0.108, 0.967) | 0.117 | ||
Liver biopsy | ||||
Fibrosis | ||||
F0 | 1 (reference) | |||
F1 | 2.625 (−18.129, 23.379) | 0.803 | ||
F2 | 4.321 (−15.918, 24.561) | 0.674 | ||
F3 | 1.288 (−18.740, 21.317) | 0.899 | ||
F4 | −0.766 (−20.821, 19.289) | 0.94 | ||
Steatosis | ||||
No steatosis | 1 (reference) | |||
Mild | −1.600 (−4.734, 1.534) | 0.315 | ||
Moderate | −1.515 (−6.960, 3.930) | 0.584 | ||
Severe | −6.865 (−13.645, −0.085) | 0.047 | ||
Inflammation | ||||
No inflammation | 1 (reference) | 1 (reference) | ||
Mild | −5.772 (−14.596, 3.051) | 0.199 | −4.631 (−12.982, 3.721) | 0.276 |
Moderate | −8.888 (−17.625, −0.151) | 0.046 | −6.553 (−14.959, 1.852) | 0.126 |
Severe | −13.894 (−22.773, −5.015) | 0.002 | −10.725 (−19.299, −2.151) | 0.014 |
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Yoo, J.-J.; Seo, Y.S.; Kim, Y.S.; Jeong, S.W.; Jang, J.Y.; Suh, S.J.; Yim, H.J.; Suk, K.T.; Kim, D.J.; Han, K.-H.; et al. The Influence of Histologic Inflammation on the Improvement of Liver Stiffness Values Over 1 and 3 Years. J. Clin. Med. 2019, 8, 2065. https://doi.org/10.3390/jcm8122065
Yoo J-J, Seo YS, Kim YS, Jeong SW, Jang JY, Suh SJ, Yim HJ, Suk KT, Kim DJ, Han K-H, et al. The Influence of Histologic Inflammation on the Improvement of Liver Stiffness Values Over 1 and 3 Years. Journal of Clinical Medicine. 2019; 8(12):2065. https://doi.org/10.3390/jcm8122065
Chicago/Turabian StyleYoo, Jeong-Ju, Yeon Seok Seo, Young Seok Kim, Soung Won Jeong, Jae Young Jang, Sang Jun Suh, Hyung Joon Yim, Ki Tae Suk, Dong Joon Kim, Kwang-Hyub Han, and et al. 2019. "The Influence of Histologic Inflammation on the Improvement of Liver Stiffness Values Over 1 and 3 Years" Journal of Clinical Medicine 8, no. 12: 2065. https://doi.org/10.3390/jcm8122065