|
Population mean: 1.33 ± 0.23 T/S |
|
TONIC treatment group |
Placebo |
1.35 ± 0.26 |
1.0 |
Metformin |
1.30 ± 0.21 |
0.29 |
Vitamin E |
1.34 ± 0.22 |
0.77 |
Demographics |
Sex |
Male |
1.32 ± 0.26 |
0.62 |
Female |
1.35 ± 0.26 |
|
Age at enrolment (years) |
− 0.24 |
< 0.001 |
Age category (years) |
< 10 |
1.42 ± 0.18 |
|
10–13 |
1.37 ± 0.25 |
0.46 |
> 13 |
1.28 ± 0.22 |
0.04 |
Mexican origin |
No |
1.31 ± 0.22 |
1.0 |
Yes |
1.35 ± 0.24 |
0.37 |
Metabolic health at baseline |
Anthropometrics |
Waist circumference (cm) |
− 0.20 |
0.01 |
Body mass index |
− 0.23 |
< 0.01 |
Birthweight (lbs) |
− 0.03 |
0.69 |
Glucose control |
Insulin (mcU/mL) |
− 0.04 |
0.62 |
Oral glucose tolerance test (OGTT), Glucose, 2 h (mg/dL) |
− 0.14 |
0.09 |
Glucose, fasting |
− 0.10 |
0.21 |
HOMA-IR |
− 0.09 |
0.27 |
HOMA-IR |
≥ 3.99 |
1.32 ± 0.23 |
0.28 |
< 3.99 |
1.37 ± 0.25 |
|
Blood pressure |
Systolic blood pressure (mmHg) |
− 0.06 |
0.44 |
Diastolic blood pressure (mmHg) |
− 0.15 |
0.07 |
Lipids |
LDL (mg/dL) |
0.08 |
0.31 |
HDL (mg/dL) |
0.03 |
0.70 |
Triglycerides (mg/dL) |
− 0.02 |
0.80 |
Total cholesterol (mg/dL) |
0.06 |
0.46 |
Liver health at baseline |
Liver function tests |
Alanine transaminase (ALT) (U/L) |
0.02 |
0.84 |
Aspartate aminotransferase (AST) (U/L) |
0.07 |
0.43 |
Alkaline phosphatase (U/L) |
0.14 |
0.09 |
Total bilirubin (mg/dL) |
− 0.10 |
0.22 |
Direct bilirubin (mg/dL) |
0.08 |
0.36 |
ALT (U/L) quartiles |
< 73 |
1.35 ± 0.25 |
1.0 |
73–90 |
1.33 ± 0.26 |
0.69 |
91–< 145 |
1.32 ± 0.22 |
0.27 |
≥ 145 |
1.34 ± 0.19 |
0.84 |
AST (U/L) quartiles |
< 43 |
1.34 ± 0.28 |
1.0 |
43–55 |
1.32 ± 0.26 |
0.69 |
56–< 78 |
1.31 ± 0.21 |
0.63 |
≥ 78 |
1.34 ± 0.19 |
0.90 |
ANA autoantibody |
Positive |
1.29 ± 0.20 |
0.34 |
Negative |
1.34 ± 0.24 |
|
General liver biopsy findings at baseline |
Steatosis baseline (increasing) |
0.07 |
0.42 |
Lobular inflammation (increasing) |
0.15 |
0.08 |
Portal inflammation (increasing) |
0.16 |
0.06 |
Fibrosis (increasing) |
0.10 |
0.24 |
Ballooning (increasing) |
− 0.04 |
0.62 |
Lobular inflammation at baseline |
0–< 2 |
1.29 ± 0.21 |
1.0 |
2–4 |
1.34 ± 0.25 |
0.17 |
> 4 |
1.47 ± 0.21 |
0.02 |
Portal inflammation at baseline |
None |
1.25 ± 0.19 |
1.0 |
Mild |
1.32 ± 0.24 |
0.30 |
More than mild |
1.41 ± 0.22 |
0.07 |
Fibrosis at baseline |
0 (none) |
1.28 ± 0.28 |
1.0 |
1 (mild-moderate Z3 peri Sinusoidal/portal-periportal) |
1.34 ± 0.22 |
0.27 |
2 (Z3 periportal) |
1.34 ± 0.22 |
0.29 |
3 (bridging) |
1.36 ± 0.24 |
0.26 |
Ballooning at baseline |
0 (none) |
1.32 ± 0.24 |
1.0 |
1 (few) |
1.38 ± 0.25 |
0.15 |
2 (many) |
1.27 ± 0.18 |
0.39 |
Steatosis at baseline |
0–1 (≤ 5–33%) |
1.29 ± 0.27 |
1.00 |
2 (34–66%) |
1.37 ± 0.20 |
0.12 |
3 (> 66%) |
1.33 ± 0.22 |
0.44 |
Steatosis location at baseline |
Zone 1-periportal |
1.35 ± 0.20 |
1.0 |
Zone 3-periportal |
1.34 ± 0.26 |
0.29 |
Azonal |
1.30 ± 0.20 |
0.12 |
Panacinar |
1.32 ± 0.23 |
0.21 |
Any NASH baseline |
No (not NASH) |
1.25 ± 0.28 |
1.0 |
Yes (borderline or definite NASH) |
1.34 ± 0.22 |
0.07 |
NASH baseline |
No NASH |
1.25 ± 0.28 |
1.0 |
Borderline |
1.36 ± 0.24 |
0.08 |
Definite NASH |
1.32 ± 0.20 |
0.23 |
NASH activity score (NAS) (ballooning + lobular + steatosis) |
0.10 |
0.25 |
Hepatic injury/necrosis specific parameters from liver biopsy |
Acidophil bodies |
Rare/absent |
1.30 ± 0.23 |
1.0 |
Many |
1.35 ± 0.23 |
0.18 |
Mallory bodies |
Rare/absent |
1.33 ± 0.23 |
1.0 |
Many |
1.18 ± 0.30 |
0.45 |
Microgranulomas |
No |
1.28 ± 0.20 |
1.0 |
Yes |
1.33 ± 0.23 |
0.64 |
Pigmented macrophages |
Rare/absent |
1.24 ± 0.16 |
1.0 |
Many |
1.33 ± 0.23 |
0.38 |
Metabolic associated characteristics from liver biopsy |
Glycogen nuclei |
Rare/absent |
1.33 ± 0.25 |
1.0 |
Many |
1.33 ± 0.22 |
0.63 |
Large lipogranulomas |
Rare/absent |
1.33 ± 0.24 |
1.0 |
Many |
1.3 4 ± 0.22 |
0.32 |
Megamitochondria |
Rare/absent |
1.33 ± 0.23 |
1.0 |
Many |
1.33 ± 0.22 |
0.8 |
Microvesicular steatosis |
Absent |
1.33 ± 0.24 |
1.0 |
Present |
1.32 ± 0.15 |
0.63 |