Table 1.
TONIC patients with leukocyte telomere length data (n = 149).
| Variable | Number | Percentage/mean (SD) |
|---|---|---|
| Leukocyte telomere length (T/S ratio) | 1.33 ± 0.23 (median 1.32 ± 0.23) | |
| TONIC treatment group | ||
| Metformin | 51/149 | 34.2% |
| Placebo | 48/149 | 66.4% |
| Vitamin E | 30/149 | 33.6% |
| Patient demographics | ||
| Age at telomere collection (years) | 13.2 ± 2.5 | |
| Age category (years) | ||
| < 10 | 14/149 | 9.4% |
| 10–13 | 58/149 | 38.9% |
| > 13 | 77/149 | 51.2% |
| Mexican origin | 86/144 | 59.7% |
| Sex at birth | ||
| Female | 29/149 | 19.5% |
| Male | 120/149 | 80.5% |
| Liver health at baseline | ||
| General liver biopsy findings | ||
| Fibrosis (baseline) | ||
| None | 35/148 | 23.7% |
| Mild Z3 | 11/148 | 7.4% |
| Moderate Z3 | 9/148 | 6.1% |
| Portal/periportal | 42/148 | 28.4% |
| Z3 periportal | 31/148 | 21.0% |
| Bridging | 20/148 | 13.5% |
| Ballooning (baseline) | ||
| Zero | 63/149 | 42.3% |
| Few | 52/149 | 34.9% |
| Many | 34/149 | 22.8% |
| Steatosis (baseline) | ||
| 0. 0–5% | 3/149 | 2.0% |
| 1. > 5–33% | 41/149 | 27.5% |
| 2. > 33–66% | 38/149 | 25.5% |
| 3. > 66% | 67/149 | 45.0% |
| Steatosis baseline (location) | ||
| Zone 1/periportal | 17/149 | 11.4% |
| Zone 3/central | 39/149 | 26.2% |
| Azonal | 16/149 | 10.7% |
| Panacinar | 77/149 | 51.7% |
| Lobular inflammation (baseline) (20× magnification) | ||
| 0 | 1/149 | 0.7% |
| < 2 | 62/149 | 41.6% |
| 2–4 | 75/149 | 50.3% |
| > 4 | 11/149 | 7.4% |
| Portal inflammation (baseline) | ||
| None | 11/149 | 7.4% |
| Mild | 120/149 | 80.5% |
| More than mild | 18/149 | 12.1% |
| NASH diagnosis at baseline | ||
| Not NASH | 25/149 | 16.8% |
| Z3 borderline | 27/149 | 18.1% |
| Z1 borderline | 36/149 | 24.2% |
| Definite NASH | 61/149 | 40.9% |
| NASH activity score (NAS) (lobular + ballooning + steatosis) | 4.58 ± 1.49 | |
| Hepatic injury/necrosis specific parameters from liver biopsy (baseline) | ||
| Acidophil bodies | ||
| None/rare | 73/149 | 49.0% |
| Many | 76/149 | 51.0% |
| Mallory bodies | ||
| None/rare | 145/149 | 97.3% |
| Many | 4/149 | 2.7% |
| Microgranuloma | ||
| None/rare | 8/149 | 5.4% |
| Many | 141/149 | 94.6% |
| Pigmented macrophages | ||
| None/rare | 5/149 | 3.4% |
| Many | 144/149 | 96.6% |
| Metabolic-associated characteristics from liver biopsy (baseline) | ||
| Glycogen nuclei | ||
| None/rare | 74/149 | 49.7% |
| Many | 75/149 | 50.3% |
| Large lipogranuloma | ||
| None/rare | 116/149 | 77.9% |
| Many | 33/149 | 22.0% |
| Megamitochondria | ||
| None/rare | 135/149 | 90.6% |
| Many | 14/149 | 9.4% |
| Microvesicular steatosis | ||
| None/rare | 138/149 | 92.6% |
| Many | 11/149 | 7.4% |
| Liver function tests and auto-antibodies | ||
| Alanine transaminase (ALT), U/L | ||
| ALT (baseline) | 120.9 ± 65.1 | |
| ALT (96 weeks) | 83.4 ± 62.8 | |
| ALT change | − 37.8 ± 72.1 | |
| Aspartate transaminase (AST), U/L | ||
| AST (baseline) | 69.9 ± 41.5 | |
| AST (96 weeks) | 51.5 ± 34.4 | |
| AST change | 19.2 ± 42.4 | |
| Alkaline phosphatase (U/L) | ||
| Alkaline phosphatase (baseline) | 223.4 ± 94.7 | |
| Alkaline phosphatase (96 weeks) | 168.2 ± 88.4 | |
| Alkaline phosphatase change | 55.9 ± 70.2 | |
| Bilirubin (mg/dL) | ||
| Total (baseline) | 0.67 ± 0.30 | |
| Total (96 weeks) | 0.73 ± 0.40 | |
| Total change | − 0.06 ± 0.31 | |
| Direct (baseline) | 0.10 ± 0.07 | |
| Direct (96 weeks) | 0.11 ± 0.08 | |
| Direct change | − 0.003 ± 0.06 | |
| Auto-antibodies | ||
| Anti-nuclear antibody (ANA positive) | 31/149 | 20.9% |
| Anti-smooth muscle Antibody (ASMA positive) | 56/149 | 37.6% |
| Anti-mitochondrial (AMA) antibody | 1/149 | 0.7% |
| Metabolic health | ||
| Anthropometrics | ||
| Body mass index (BMI) (kg/m2) | ||
| Baseline | 33.9 ± 6.0 | |
| 96 weeks follow-up | 35.5 ± 6.3 | |
| BMI change (baseline to follow-up) | 1.85 ± 3.0 | |
| Waist circumference (cm) | ||
| Baseline | 108.2 ± 14.7 | |
| 96 weeks (follow-up) | 113.2 ± 15.0 | |
| Waist change (cm) | 5.2 ± 9.1 | |
| Systolic blood pressure (mmHg) | 125.0 ± 15.5 | |
| Diastolic blood pressure (mmHg) | 69.4 ± 11.2 | |
| Glucose control | ||
| Glucose (fasting), mg/dL | 89.1 ± 9.6 | |
| Insulin (fasting), mcU/mL | 42.3 ± 50.4 | |
| Glucose tolerance (OGTT) | ||
| Test 2 h (mg/dL) | 119.8 ± 25.8 | |
| HOMA-IR | 9.03 ± 11.9 | |
| ≥ 3.99 ml/DL | 117/149 | 78.5% |
| < 3.99 ml/DL | 32/149 | 21.5% |
| Lipids | ||
| LDL (mg/dL) | 107.0 ± 30.6 | |
| HDL (mg/dL) | 37.0 ± 7.9 | |
| Triglycerides (mg/dL) | 149.2 ± 96.6 | |
| Total cholesterol (mg/dL) | 173.3 ± 40.2 | |