Retrospective Study
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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 27, 2021; 13(7): 790-803
Published online Jul 27, 2021. doi: 10.4254/wjh.v13.i7.790
Table 1 General characteristics of study population
All participants (n = 740) Age 15 (13-16) Sex, n (%) Male 386 (52.16) Female 354 (47.84) Race, n (%) Mexican American 130 (17.57) Other Hispanic 55 (7.43) Non-Hispanic White 229 (30.95) Non-Hispanic Black 171 (23.11) Non-Hispanic Asian 83 (11.22) Other race-including multi-racial 72 (9.73) Smoking, n (%) 6 (0.84) Steatosis grade, n (%) S0 538 (72.8) S1 63 (8.53) S2 39 (5.28) S3 99 (13.4) Fibrosis result, n (%) F0-F1 693 (93.65) F2 26 (3.51) F3 12 (1.62) F4 9 (1.22) Waist-to-height ratio 0.48 (0.43-0.55) Waist-to-hip ratio 0.57 (0.53-0.63) Body mass index, n (%) Underweight 4 (0.54) Normal 392 (53.33) Risk of overweight 128 (17.41) Overweight 211 (28.71) Days physically active at least 60 min 4 (2-5) Hours/day watch TV or videos past 30 d, n (%) Less than 1 h 107 (14.72) 1 h 121 (16.64) 2 h 166 (22.83) 3 h 105 (14.44) 4 h 78 (10.73) 5 h or more 150 (20.63) Hours/day use computer past 30 d, n (%) Less than 1 h 68 (9.34) 1 h 85 (11.68) 2 h 131 (17.99) 3 h 83 (11.4) 4 h 100 (13.74) 5 h or more 261 (35.85)
Table 2 Univariate Analysis of participant characteristics and steatosis grade
Steatosis grade Coefficient P value S0 (n = 538) S1 (n = 63) S2 (n = 39) S3 (n = 99) Age 14 (13-16) 14 (13-16) 15 (14-16) 15 (14-16) 0.0562 0.016a Sex Male 273 (50.74%) 29 (46.03%) 20 (51.28%) 64 (64.65%) 0.1747 0.027 a Female 265 (49.26%) 34 (53.97%) 19 (48.72%) 35 (35.35%) Race Mexican American 82 (15.24%) 11 (17.46%) 7 (17.95%) 30 (30.3%) 0.3542 < 0.001a Other Hispanic 42 (7.81%) 5 (7.94%) 1 (2.56%) 7 (7.07%) -0.0903 0.549 Non-Hispanic White 178 (33.09%) 18 (28.57%) 13 (33.33%) 20 (20.2%) -0.2008 0.019 a Non-Hispanic Black 128 (23.79%) 10 (15.87%) 11 (28.21%) 21 (21.21%) -0.0440 0.640 Non-Hispanic Asian 60 (11.15%) 8 (12.7%) 4 (10.26%) 11 (11.11%) -0.0026 0.983 Other Race-Including Multi-Racial 48 (8.92%) 11 (17.46%) 3 (7.69%) 10 (10.1%) 0.0666 0.618 Smoking 4 (0.77%) 1 (1.59%) 0 (0%) 1 (1.04%) 0.0732 0.868 Waist-to-height ratio 0.45 (0.42-0.51) 0.54 (0.47-0.59) 0.57 (0.48-0.62) 0.6 (0.55-0.66) 6.5565 < 0.001a Waist-to-hip ratio 0.56 (0.52-0.6) 0.6 (0.57-0.65) 0.63 (0.57-0.68) 0.64 (0.61-0.69) 6.6835 < 0.001a Body mass index 0.6128 < 0.001a Underweight 4 (0.75%) 0 (0%) 0 (0%) 0 (0%) Normal 349 (65.48%) 22 (34.92%) 10 (25.64%) 10 (10.1%) Risk of overweight 97 (18.2%) 14 (22.22%) 8 (20.51%) 9 (9.09%) Overweight 83 (15.57%) 27 (42.86%) 21 (53.85%) 80 (80.81%) Days physically active at least 60 min 4 (2-6) 3.5 (1-5) 4 (2-5) 4 (2-5) -0.0167 0.348 Hours/day watch TV or videos past 30 d 2 (1-4) 2 (1-4) 3 (1.75-5) 2 (1-4.25) 0.0421 0.070 Hours/day use computer past 30 d 3 (2-5) 4 (2-5) 5 (2-5) 4 (2-5) 0.0560 0.014a Diet Energy (1000 kcal) 1.82 (1.43-2.45) 1.75 (1.26-2.28) 1.62 (1.33-2) 1.71 (1.34-2.38) -0.0732 0.145 Protein (mg) 63.59 (48.32-86.06) 63.15 (40.29-77.27) 53.38 (37.92-80.78) 64.1 (49.36-87.48) -0.0732 0.145 Carbohydrate (mg) 230.94 (180.54-301.73) 233.36 (154.21-296.51) 213.08 (169.63-253.71) 219.06 (173.09-290.58) -0.0005 0.178 Total sugars (mg) 94.74 (67.04-133.77) 89.84 (54.32-140.86) 75.37 (51.43-97.67) 90.5 (63.35-127.21) -0.0008 0.224 Dietary fiber (mg) 12.85 (9.25-17.36) 12.2 (8.77-18.3) 12.5 (9.24-16.79) 12.2 (8.8-16.4) -0.0051 0.368 Total fat (mg) 75.09 (55.41-97.52) 66.13 (43.61-93.44) 62.68 (45.53-83.34) 71.58 (47.42-95.31) -0.0016 0.143 Total saturated fatty acids (mg) 25.07 (17.39-35.43) 24.43 (11.47-32.25) 18.7 (11.7-30.89) 22.91 (14.97-31.11) -0.0044 0.122 Cholesterol (mg) 197 (132.88-320.5) 165 (90.25-305.5) 162 (72.38-283.63) 199 (134-279.25) -0.0003 0.254 Systolic blood pressure (mm Hg) 106 (100-114) 108 (103.5-114.5) 112 (104-120) 112 (104-120) 0.0254 < 0.001a Diastolic blood pressure (mm Hg) 62 (54-68) 60 (51.5-68) 62 (55.5-70) 60 (54-66) -0.0038 0.222 Triglycerides, refrig serum (mg/dL)1 74 (57-98) 79 (62-103) 78.5 (70-105.5) 98 (68-159) 0.0051 < 0.001a Uric acid (mg/dL) 4.7 (4-5.6) 5.1 (4.15-6.05) 5.45 (4.65-6.15) 5.75 (4.7-6.7) 0.1984 < 0.001a Aspartate aminotransferase (IU/L)1 18 (16-22) 18 (15.25-21.75) 16.5 (15-21) 20.5 (18-27) 0.0151 0.002a Alanine aminotransferase (IU/L)1 12 (10-15) 15 (11.25-19) 14 (10-17.5) 20.5 (14-34) 0.0372 < 0.001a Gamma glutamyl transferase (IU/L)1 12 (10-15) 12 (10-18.75) 15.5 (10-19) 18 (12-24) 0.0375 < 0.001a Alkaline phosphatase (ALP) (IU/L) 130 (87-225.75) 121 (86.75-235) 135 (75.5-188) 126.5 (99-188) -0.0003 0.537 Total bilirubin (mg/dL)1 0.4 (0.3-0.6) 0.3 (0.23-0.48) 0.4 (0.3-0.5) 0.4 (0.3-0.4) -0.3419 0.009a Total protein (g/dL) 7.3 (7-7.5) 7.3 (7-7.5) 7.35 (7.15-7.6) 7.35 (7.2-7.6) 0.3620 0.002a Albumin, refrigerated serum (g/dL) 4.3 (4.1-4.5) 4.3 (4.1-4.5) 4.25 (4.05-4.45) 4.2 (4-4.4) -0.5553 < 0.001a Iron frozen, serum (μg/dL) 85 (61-113) 86 (58.25-105.75) 69 (49.5-85.75) 75 (56-103) -0.0027 0.013a Total iron binding capacity (μg/dL) 348 (317.5-382) 366 (342-392.25) 360 (326.25-406.5) 356 (322-385) 0.0015 0.092 Transferrin Saturation (%) 24 (17-33) 23 (15.25-30.75) 19 (13.5-26) 22.5 (15-30) -0.0104 0.004a Ferritin (ng/mL) 39.2 (24.85-59.85) 35.25 (18.75-57.5) 30.85 (14.65-60.15) 59.2 (35-93.12) 0.0038 < 0.001a Total cholesterol (mg/dL) 150 (134-168) 158 (132.75-174) 152 (139.5-166.25) 157 (139.25-178.75) 0.0032 0.035a Low-density lipoprotein cholesterol (mg/dL) 78.8 (64.8-94.6) 85.8 (69.15-107.45) 82.5 (70.1-97.8) 87 (70.6-103.6) 0.0041 0.019a Direct high-density lipoprotein cholesterol (mg/dL) 53 (46-61) 50 (46-56) 48 (41.5-55) 44 (39-51) -0.0238 < 0.001a HS C-reactive protein (mg/L)1 0.49 (0.32-1.01) 0.72 (0.35-1.51) 0.95 (0.43-1.89) 1.76 (0.87-3.74) 0.0448 < 0.001a Platelet count (1000 cells/uL) 258 (228-292) 269 (228.5-318.5) 273 (239-307) 282 (248-313) 0.0026 < 0.001a Hemoglobin A1c (%)1 5.3 (5.1-5.5) 5.3 (5.1-5.45) 5.3 (5.1-5.6) 5.4 (5.2-5.5) 0.2280 0.054 Fasting glucose (mg/dL) 97 (93-101) 98 (93.25-101.75) 101 (94-103) 99.5 (96-103) 0.0219 0.017a Insulin (pmol/L) 54.96 (39.84-79.38) 101.1 (71.58-130.8) 88.32 (62.28-118.14) 129.63 (75.66-185.46) 0.0086 < 0.001a Homeostatic model assessment for insulin resistance 2.23 (1.58-3.32) 4.08 (2.96-5.47) 3.56 (2.64-4.96) 5.34 (3.08-7.78) 0.1976 < 0.001a
Table 3 Predictors of steatosis grade in multivariate level
Predictors Coefficient (standard error) P value Alanine aminotransferase (IU/L)1 0.3912 (0.1159) 0.001 Homestatic model assessment for insulin resistance 0.0684 (0.0247) 0.006 Waist-to-height ratio 3.2299 (0.0912) 0.001 Body mass index 0.2335 (0.0912) 0.011
Table 4 Univariate Analysis of participant characteristics and fibrosis stage
Fibrosis stage Coefficient P value F0 - F1 (n = 693) F2 (n = 26) F3 (n = 12) F4 (n = 9) Age 15 (13-16) 15 (13-17) 14 (13-15) 15 (14.75-17) 0.0106 0.276 Sex Male 356 (51.37%) 17 (65.38%) 6 (50%) 7 (77.78%) 0.0533 0.105 Female 337 (48.63%) 9 (34.62%) 6 (50%) 2 (22.22%) Race Mexican American 123 (17.75%) 4 (15.38%) 0 (0%) 3 (33.33%) -0.0049 0.909 Other Hispanic 53 (7.65%) 1 (3.85%) 1 (8.33%) 0 (0%) -0.0535 0.393 Non-Hispanic White 222 (32.03%) 3 (11.54%) 2 (16.67%) 2 (22.22%) -0.0685 0.054 Non-Hispanic Black 148 (21.36%) 13 (50%) 8 (66.67%) 2 (22.22%) 0.1309 < 0.001a Non-Hispanic Asian 78 (11.26%) 4 (15.38%) 0 (0%) 1 (11.11%) -0.0222 0.669 Other Race-Including Multi-Racial 69 (9.96%) 1 (3.85%) 1 (8.33%) 1 (11.11%) -0.0230 0.679 Smoking 5 (0.75%) 0 (0%) 0 (0%) 1 (11.11%) 0.3967 0.032a Waist-to-height ratio 0.48 (0.43-0.55) 0.49 (0.44-0.61) 0.49 (0.4-0.61) 0.5 (0.42-0.68) 0.3746 0.042a Waist-to-hip ratio 0.57 (0.53-0.62) 0.59 (0.54-0.69) 0.6 (0.52-0.64) 0.59 (0.5-0.7) 0.2804 0.215 Body mass index 0.0330 0.079 Underweight 4 (0.58%) 0 (0%) 0 (0%) 0 (0%) Normal 370 (53.78%) 11 (42.31%) 6 (50%) 5 (55.56%) Risk of overweight 126 (18.31%) 2 (7.69%) 0 (0%) 0 (0%) Overweight 188 (27.33%) 13 (50%) 6 (50%) 4 (44.44%) Days physically active at least 60 min 4 (2-5) 4 (2-5) 2.5 (0.5-6) 5 (2.5-6) -0.0039 0.597 Hours/day watch TV or videos past 30 d 2 (1-4) 2 (1-4) 2.5 (2-4.5) 2 (0-3.5) -0.0027 0.779 Hours/day use computer past 30 d 3 (2-5) 5 (3-5) 4 (2.5-5) 3 (0.75-5) 0.0062 0.519 Steatosis grade 0.0757 < 0.001a S0 518 (74.86%) 13 (50%) 3 (25%) 4 (44.44%) S1 57 (8.24%) 2 (7.69%) 3 (25%) 1 (11.11%) S2 35 (5.06%) 2 (7.69%) 2 (16.67%) 0 (0%) S3 82 (11.85%) 9 (34.62%) 4 (33.33%) 4 (44.44%) Diet Energy (1000 kcal) 1.8 (1.4-2.42) 1.5 (1.37-2.11) 1.62 (1.4-1.75) 1.75 (1.32-2.4) -0.0225 0.282 Protein (mg) 63.69 (46.81-85.41) 50.66 (42.74-94.29) 59.33 (45.9-76.55) 68.03 (49.61-73.78) -0.0004 0.405 Carbohydrate (mg) 230.55 (174.26-299.84) 202.56 (152.11-255.23) 204.26 (177.87-238.7) 242.27 (186.12-305.52) -0.0001 0.671 Total sugars (mg) 92.59 (64.25-133.63) 87.43 (58.07-120.32) 75.76 (62.31-94.74) 94.74 (85.8-123.02) -0.0001 0.697 Dietary fiber (mg) 12.7 (9.25-17.1) 10.8 (7.62-17.64) 10.4 (9.02-14.29) 12.85 (10.8-16.96) -0.0018 0.461 Total fat (mg) 74.07 (52.04-97.34) 55.7 (45.07-79.29) 65.98 (50.43-78.07) 69.09 (45.95-97.94) -0.0007 0.091 Total saturated fatty acids (mg) 24.72 (16.8-34.81) 21.06 (14.84-29.88) 23.04 (18.87-27.64) 22.84 (18.35-28.35) -0.0020 0.083 Cholesterol (mg) 197 (129.13-317.63) 150.5 (85-213.25) 162.5 (118.38-228.88) 146.5 (124.75-310.25) -0.0002 0.065 Systolic blood pressure (mmHg) 106 (102-114) 108 (103.5-126.5) 108 (100.5-120) 116 (113-122) 0.0066 < 0.001a Diastolic blood pressure (mmHg) 62 (54-68) 64 (53-71) 56 (50.5-65.5) 60 (56-68) -0.0001 0.967 Triglycerides, refrig serum (mg/dL)1 78 (61-104) 67.5 (50-111) 88 (61.75-161) 88.5 (56.5-121.5) 0.0276 0.471 Uric acid (mg/dL) 4.9 (4.1-5.8) 5 (3.7-6) 4.7 (3.3-5.98) 5.75 (4.2-7.45) 0.0079 0.560 Aspartate aminotransferase (IU/L)1 18 (16-22) 18 (15-25) 15 (14-23) 29 (20-32) 0.0882 0.137 Alanine aminotransferase (IU/L)1 13 (10-17) 14 (9-20) 12 (9.5-15) 20.5 (15-37.5) 0.0738 0.046a Gamma glutamyl transferase (IU/L)1 13 (10-17) 12 (9-16) 12 (10-19.5) 20.5 (14-32.5) 0.0047 0.018a Alkaline phosphatase (IU/L) 129 (88-222.5) 121.5 (81-205) 187 (127.75-242.75) 113 (105-129.5) -0.0001 0.470 Total bilirubin (mg/dL)1 0.4 (0.3-0.5) 0.3 (0.2-0.6) 0.4 (0.3-0.5) 0.45 (0.35-0.7) 0.0178 0.577 Total protein (g/dL) 7.3 (7-7.5) 7.15 (6.8-7.3) 7.3 (7-7.63) 7.2 (7.15-7.45) -0.0156 0.745 Albumin, refrigerated serum (g/dL) 4.3 (4.1-4.5) 4.05 (3.8-4.4) 4.2 (4.03-4.3) 4.3 (4.1-4.65) -0.0744 0.229 Iron frozen, Serum (μg/dL) 83 (59-112) 80.5 (47-88) 88 (68-106) 67.5 (58-120.5) 0.0001 0.777 Total iron binding capacity (μg/dL) 352 (322-387) 346 (314-378) 355 (315.25-375.25) 314 (310-327.5) -0.0009 0.018a Transferrin saturation (%) 23 (17-32) 22 (15-26) 28 (19.25-31.5) 20 (18-39) 0.0013 0.377 Ferritin (ng/mL) 39.3 (24.5-62.1) 45.55 (24.45-61.85) 56.25 (29-71) 102.35 (35.75-141) 0.0009 0.030a Total cholesterol (mg/dL) 151 (134-171) 140.5 (136-156) 161 (143-175) 131 (119-147.5) -0.0010 0.102 Low-density lipoprotein cholesterol (mg/dL) 81 (66.2-97.6) 77.5 (64.2-92.6) 88.2 (71.6-91.4) 57.2 (55.5-80.1) -0.0013 0.082 Direct high-density lipoprotein cholesterol (mg/dL) 51 (44-59) 49.5 (44-58) 50 (46-62) 49.5 (39-56) -0.0012 0.426 HS C-reactive protein (mg/L)1 0.57 (0.35-1.39) 0.83 (0.34-1.34) 0.72 (0.37-1.12) 0.97 (0.53-7.09) 0.0240 0.134 Platelet count (1000 cells/uL) 262 (230-297.5) 275.5 (242-302.5) 262.5 (226-277) 262.5 (234-275) -0.0001 0.769 Hemoglobin A1c (%)1 5.3 (5.1-5.5) 5.3 (5.25-5.6) 5.45 (5.25-5.65) 5.35 (5.15-5.6) 0.4629 0.098 Fasting glucose (mg/dL) 98 (94-102) 99 (94-103) 101 (95.5-104.25) 92 (89.75-95.75) -0.0031 0.490 Insulin (pmol/L) 64.83 (43.38-99) 70.26 (45.87-183.17) 87.06 (59.28-160.28) 51.42 (27.29-127.14) 0.0005 0.291 Homeostatic model assessment for insulin resistance 2.61 (1.71-3.96) 2.66 (1.96-7.9) 4.08 (2.34-6.66) 1.95 (1.1-4.95) 0.0101 0.383
Table 5 Predictors of fibrosis stage in multivariate level
Predictors Coefficient (standard error) P value Steatosis grade 0.0730 (0.0172) < 0.001 Race: Non-Hispanic Black 0.1352 (0.0430) 0.002 Smoke 0.4065 (0.1845) 0.028 Systolic blood pressure (mmHg) 0.0040 (0.0019) 0.035
Table 6 Predictive performance of liver fibrosis indices
Liver fibrosis indices (Predictor) Outcome Predictive performance Index Cutoff Accuracy PPV NPV Sensitivity Specificity APRI 0.7 F4 98.45% 0% 98.8% 0.0% 99.7% FIB4 1.3 F4 98.61% 0% 98.8% 0.0% 99.8% PNFI 9 F4 85.31% 3.26% 99.1% 37.5% 85.9% PNFI 3 S1-S3 85.60% 83.33% 86.2% 59.7% 95.5%