Background
Methods
Participant recruitment
Definition of NAFLD
Non-invasive markers of NAFLD
Mortality follow-up
Definition of diabetes, hypertension, and MetS
Statistical analysis
Results
Cross-sectional NAFLD prediction cohort
Characteristics | No NAFLD (n = 4,117) | NAFLD (n = 1,067) |
Pvalue | ||
---|---|---|---|---|---|
Value | 95% CI | Value | 95% CI | ||
Age, years | 40.42 | 39.59 to 41.25 | 45.32 | 43.97 to 46.67 | <0.001 |
Female sex, % | 52.6 | 50.4 to 54.7 | 45.6 | 41.7 to 49.5 | 0.005 |
Race/ethnicity, % | <0.001 | ||||
Non-Hispanic white | 74.9 | 71.2 to 78.3 | 73.6 | 69.6 to 77.3 | |
Non-Hispanic black | 11.6 | 10.1 to 13.4 | 8.7 | 7.3 to 10.3 | |
Mexican-American | 4.7 | 3.7 to 5.8 | 7.6 | 6.2 to 9.3 | |
Other | 8.8 | 6.5 to 11.8 | 10.1 | 7.3 to 13.8 | |
Education | 0.001 | ||||
< High school | 5.5 | 4.2 to 7.1 | 8.4 | 6.4 to 11.1 | |
High school | 14.1 | 12.5 to 16.0 | 18.9 | 15.6 to 22.8 | |
> High school | 80.4 | 77.7 to 82.8 | 72.6 | 67.8 to 77.0 | |
Smoking | <0.001 | ||||
Never | 48.6 | 46.2 to 51.1 | 41.9 | 38.1 to 45.7 | |
Former | 23.2 | 21.5 to 25.1 | 32.8 | 29.4 to 36.5 | |
Current | 28.1 | 25.8 to 30.6 | 25.3 | 21.7 to 29.3 | |
Diabetes, % | 1.9 | 1.6 to 2.2 | 9.8 | 7.6 to 12.5 | <0.001 |
Hypertension, % | 16.0 | 14.6 to 17.6 | 33.7 | 29.9 to 37.6 | <0.001 |
Lipid-lowering medication, % | 2.4 | 1.8 to 3.0 | 5.0 | 3.4 to 7.1 | <0.001 |
History of CVD, % | 1.8 | 1.3 to 2.3 | 3.9 | 2.8 to 5.4 | 0.002 |
Metabolic syndrome, % | 16.9 | 15.3 to 18.7 | 54.8 | 51.2 to 58.5 | <0.001 |
Abdominal obesity, % | 28.0 | 26.5 to 29.5 | 65.2 | 61.3 to 68.9 | <0.001 |
Hypertriglyceridemia, % | 22.8 | 20.5 to 25.3 | 54.3 | 50.4 to 58.2 | <0.001 |
Impaired fasting glucose, % | 20.1 | 18.5 to 21.8 | 42.1 | 38.4 to 46.0 | <0.001 |
Low HDL level, % | 35.50 | 32.7 to 38.5 | 60.1 | 54.9 to 65.0 | <0.001 |
Body mass index, kg/m2
| 25.72 | 25.51 to 25.93 | 30.29 | 29.76 to 30.82 | <0.001 |
Waist circumference, cm | 88.82 | 88.35 to 89.3 | 101.75 | 100.36 to 103.13 | <0.001 |
Serum cholesterol, mg/dl | 199.83 | 198.5 to 201.17 | 208.63 | 205.63 to 211.63 | <0.001 |
Serum triglycerides, mg/dl | 117.71 | 114.18 to 121.24 | 192.30 | 183.44 to 201.15 | <0.001 |
Serum HDL cholesterol, mg/dl | 51.04b
| 50.15 to 51.93 | 42.91d
| 41.67 to 44.15 | <0.001 |
Plasma glucose, mg/dl | 94.07c
| 93.41 to 94.73 | 104.95 | 102.56 to 107.33 | <0.001 |
Serum insulin, μU/ml | 8.80 | 8.54 to 9.06 | 16.09 | 14.85 to 17.33 | <0.001 |
SBP, mmHg | 118.42 | 117.55 to 119.3 | 125.7e
| 124.7 to 126.7 | <0.001 |
AST, U/L | 19.60 | 19.21 to 20 | 25.24 | 24.31 to 26.17 | <0.001 |
ALT, U/L | 15.70 | 15.03 to 16.36 | 25.68 | 24.27 to 27.09 | <0.001 |
GGT, U/L | 24.42 | 23.69 to 25.15 | 41.61 | 37.77 to 45.44 | <0.001 |
FLI | 34.70 | 33.41 to 35.99 | 67.56 | 64.92 to 70.2 | <0.001 |
HSI | 33.10 | 32.7 to 33.49 | 39.26 | 38.64 to 39.89 | <0.001 |
LFS | 1.92 | 2.03 to to 1.82 | 0.21 | 0.04 to 0.46 | <0.001 |
Liver fat percentage, % | 2.45 | 2.33 to 2.56 | 5.88 | 5.49 to 6.27 | <0.001 |
LAP | 39.74 | 38.08 to 41.40 | 91.71 | 86.35 to 97.06 | <0.001 |
NAFLD prediction scores | All participants (n = 5,184; 1067 cases) | Non-Hispanic white (n = 1,953; 376 cases) | Non-Hispanic black (n = 1,577; 244 cases) | Mexican-American (n = 1,409; 401 cases) | Others (n = 245; 46 cases) | |||||
---|---|---|---|---|---|---|---|---|---|---|
AUC | 95% CI | AUC | 95% CI | AUC | 95% CI | AUC | 95% CI | AUC | 95% CI | |
LFS | 0.771 | 0.754 to 0.787 | 0.78 | 0.753 to 0.808 | 0.711 | 0.674 to 0.748 | 0.781 | 0.754 to 0.808 | 0.865 | 0.804 to 0.926 |
FLI | 0.757 | 0.74 to 0.774 | 0.778 | 0.75 to 0.807 | 0.706 | 0.668 to 0.745 | 0.764 | 0.737 to 0.791 | 0.788 | 0.708 to 0.867 |
LAP | 0.741 | 0.723 to 0.758 | 0.767 | 0.739 to 0.795 | 0.694 | 0.654 to 0.733 | 0.726 | 0.698 to 0.755 | 0.761 | 0.683 to 0.84 |
HSI | 0.732 | 0.714 to 0.749 | 0.735 | 0.705 to 0.764 | 0.673 | 0.635 to 0.711 | 0.760 | 0.733 to 0.787 | 0.779 | 0.705 to 0.854 |
NAFLD definition | Non-invasive NAFLD score | Cutoff point | SP, % | 95% CI, % | SN, % | 95% CI, % | Reported SP, % | Reported SN, % | Ref | |
---|---|---|---|---|---|---|---|---|---|---|
No to mild versus intermediate to severe steatosis) | LFS | Inclusion | 1.257 | 96.43 | 95.82 to 96.98 | 26.34 | 23.71 to 29.09 | 95 | 51 | [7] |
Exclusion | ≤ −1.413 | 67.94 | 66.49 to 69.36 | 73.95 | 71.20 to 76.56 | 52 | 95 | |||
FLI | Inclusion | 60 | 73.60 | 72.22 to 74.94 | 67.48 | 64.58 to 70.29 | 86 | 61 | [6] | |
Exclusion | <30 | 48.77 | 47.24 to 50.31 | 84.44 | 82.13 to 86.57 | 64 | 87 | |||
HSI | Inclusion | 36 | 69.35 | 67.91 to 70.75 | 66.26 | 63.33 to 69.10 | 92 | 46 | [9] | |
Exclusion | <30 | 29.75 | 28.36 to 31.18 | 91.38 | 89.53 to 92.99 | 40 | 92.50 |
Prospective mortality prediction cohort
Characteristics | Low LFS (n = 3,524) | Intermediate LFS (n = 1,890) | High LFS (n = 478) |
Pvalue | |||
---|---|---|---|---|---|---|---|
Value | 95% CI | Value | 95% CI | Value | 95% CI | ||
Age, years | 39.23 | 38.34 to 40.13 | 45.50 | 44.28 to 46.71 | 45.04 | 42.78 to 47.29 | <0.001 |
Sex, female % | 56.40 | 54.1 to 58.7 | 42.30 | 39.3 to 45.3 | 45.70 | 38.1 to 53.5 | <0.001 |
Race/ethnicity, % | <0.001 | ||||||
Non-Hispanic white | 78.40 | 75.5 to 81.1 | 74.10 | 69.3 to 78.4 | 73.30 | 68.0 to 78.0 | <0.001 |
Non-Hispanic black | 10.30 | 8.9 to 11.8 | 10.50 | 8.8 to 12.5 | 10.90 | 8.6 to 13.7 | <0.001 |
Mexican-American | 4.20 | 3.5 to 5.1 | 6.40 | 5.1 to 8.0 | 7.80 | 5.3 to 11.2 | <0.001 |
Other | 7.10 | 5.4 to 9.3 | 9.00 | 5.9 to 13.4 | 8.00 | 5.6 to 11.5 | <0.001 |
Education, % | <0.001 | ||||||
< High school | 4.10 | 3.2 to 5.2 | 8.20 | 6.0 to 11.0 | 8.10 | 5.5 to 11.7 | <0.001 |
High school | 13.30 | 11.7 to 15.0 | 18.80 | 15.6 to 22.4 | 16.80 | 13.8 to 20.3 | <0.001 |
> High school | 82.60 | 80.3 to 84.7 | 73.10 | 68.4 to 77.3 | 75.10 | 70.1 to 79.6 | <0.001 |
Smoking, % | <0.001 | ||||||
Never | 49.20 | 46.2 to 52.3 | 41.00 | 37.3 to 44.8 | 47.90 | 40.3 to 55.5 | <0.001 |
Former | 21.60 | 19.6 to 23.7 | 33.20 | 29.5 to 37.1 | 32.30 | 25.9 to 39.5 | <0.001 |
Current | 29.20 | 26.4 to 32.2 | 25.80 | 23.1 to 28.6 | 19.80 | 14.1 to 27.1 | <0.001 |
Diabetes, % | 0.20 | 0.1 to 0.3 | 5.70 | 4.6 to 7.0 | 26.20 | 21.3 to 31.7 | <0.001 |
Hypertension, % | 10.00 | 8.7 to 11.4 | 32.70 | 29.6 to 36.0 | 45.40 | 39.6 to 51.3 | <0.001 |
Lipid-lowering medication, % | 1.10 | .7 to 1.8 | 5.40 | 4.1 to 7.1 | 7.20 | 4.4 to 11.6 | <0.001 |
History of CVD, % | 1.30 | .9 to 1.9 | 3.40 | 2.4 to 4.8 | 5.10 | 3.1 to 8.2 | <0.001 |
Poverty income ratio | 3.25 | 3.09 to 3.4 | 2.98 | 2.76 to 3.2 | 2.83 | 2.54 to 3.11 | 0.003 |
Waist circumference, cm | 85.22 | 84.74 to 85.71 | 100.22 | 99.52 to 100.92 | 112.22 | 110.51 to 113.93 | <0.001 |
Dietary caffeine intake, mg | 272.81 | 251.75 to 293.87 | 276.43 | 234.41 to 318.45 | 216.06 | 189.12 to 243 | 0.222 |
Serum cholesterol, mg/dl | 196.06 | 194.01 to 198.11 | 213.02 | 209.91 to 216.14 | 218.33 | 211.56 to 225.1 | <0.001 |
Serum HDL cholesterol, mg/dl | 53.38 | 52.51 to 54.25 | 43.81 | 42.74 to 44.89 | 39.06 | 37.89 to 40.23 | <0.001 |
Serum transferrin saturation, % | 27.78 | 27.25 to 28.31 | 26.25 | 25.55 to 26.95 | 25.54 | 23.88 to 27.2 | <0.001 |
Serum C-reactive protein, mg/dl | 0.33 | 0.31 to 0.35 | 0.45 | 0.42 to 0.49 | 0.58 | 0.5 to 0.66 | <0.001 |
Drinks/weeka
| 2.68 | 2.45 to 2.9 | 2.32 | 2.01 to 2.64 | 1.62 | 1.11 to 2.13 | <0.001 |
LFS | -2.53 | -2.58 to -2.48 | -0.41 | -0.46 to -0.36 | 3.20 | 2.83 to 3.57 | <0.001 |
Mortality | |||||||
All causes | 8.90 | 7.7 to 10.2 | 13.60 | 11.4 to 16.2 | 17.70 | 12.9 to 23.9 | <0.001 |
CVD-related | 2.80 | 2.3 to 3.5 | 5.10 | 4.0 to 6.4 | 9.00 | 5.4 to 14.8 | <0.001 |
Liver-related | 0.10 | 0.0 to 0.3 | 0.10 | 0.0 to 0.2 | 1.20 | 0.3 to 5.2 | 0.069 |
Diabetes-related | 0.20 | 0.1 to 0.5 | 0.90 | 0.6 to 1.5 | 3.90 | 2.0 to 7.4 | <0.001 |
Malignancy-related | 2.80 | 2.1 to 3.8 | 3.60 | 2.5 to 5.2 | 2.00 | 1.0 to 4.2 | 0.698 |
Mortality from: | Simple modela
| Full modelb
| Full model + NFS adjustmentb
| ||||||
---|---|---|---|---|---|---|---|---|---|
HR | 95% CI |
Pvalue | HR | 95% CI |
Pvalue | HR | 95% CI |
Pvalue | |
All causes | |||||||||
Low (ref) versus high LFS | 1.51 | 0.99 to 2.3 | 0.056 | 1.59 | 0.93 to 2.72 | 0.087 | 1.65 | 0.96 to 2.85 | 0.07 |
Int (ref) versus high LFS | 1.52 | 1.03 to 2.23 | 0.034 | 1.60 | 1.01 to 2.54 | 0.048 | 1.61 | 1 to 2.58 | 0.049 |
LFS (continuous) | 1.07 | 0.99 to 1.14 | 0.082 | 1.09 | 1.01 to 1.19 | 0.039 | 1.1 | 1.024 to 1.19 | 0.011 |
CVD | |||||||||
Low (ref) versus high LFS | 2.29 | 1.24 to 4.26 | 0.009 | 2.24 | 1.03 to 4.88 | 0.042 | 2.30 | 1.02 to 5.19 | 0.046 |
Int (ref) versus high LFS | 2.20 | 1.18 to 4.12 | 0.015 | 2.30 | 1.19 to 4.48 | 0.015 | 2.32 | 1.18 to 4.55 | 0.015 |
LFS (continuous) | 1.11 | 1.04 to 1.19 | 0.002 | 1.11 | 1.03 to 1.19 | 0.006 | 1.13 | 1.05 to 1.21 | <0.001 |
Liver disease | |||||||||
Low (ref) versus high LFS | 9.80 | 2.01 to 47.62 | 0.006 | 31.25 | 3.13 to 333.33 | 0.004 | 46.45 | 5.13 to 420.51 | <0.001 |
Int (ref) versus high LFS | 17.24 | 2.6 to 111.11 | 0.004 | 30.30 | 4-250 | 0.001 | 32.99 | 4.57 to 237.95 | <0.001 |
LFS (continuous) | 1.25 | 1.14 to 1.36 | <0.001 | 1.32 | 1.12 to 1.55 | 0.001 | 1.3 | 1.12 to 1.51 | <0.001 |
Diabetes | |||||||||
Low (ref) versus high LFS | 15.87 | 6.02 to 41.67 | <0.001 | 2.87 | 0.65 to 12.66 | 0.161 | 3.13 | 0.67 to 14.56 | 0.143 |
Int (ref) versus high LFS | 5.24 | 2.24 to 12.2 | <0.001 | 1.98 | 0.71 to 5.52 | 0.185 | 2.04 | 0.72 to 5.79 | 0.176 |
LFS (continuous) | 1.37 | 1.27 to 1.48 | <0.001 | 1.21 | 1.02 to 1.44 | 0.034 | 1.21 | 1.03 to 1.42 | 0.024 |
Malignancy | |||||||||
Low (ref) versus high LFS | 0.55 | 0.25 to 1.24 | 0.147 | 0.75 | 0.27 to 2.11 | 0.578 | 0.75 | 0.27 to 2.09 | 0.576 |
Int (ref) versus high LFS | 0.65 | 0.29 to 1.44 | 0.281 | 0.76 | 0.32 to 1.79 | 0.519 | 0.76 | 0.32 to 1.79 | 0.518 |
LFS (continuous) | 0.92 | 0.86 to 0.99 | 0.026 | 0.97 | 0.87 to 1.07 | 0.521 | 0.95 | 0.8 to 1.12 | 0.495 |