Table 2.
Non-invasive quantitative biomarkers with which to probe NAFLD, NASH and fibrosis burden. NFS = NAFLD fibrosis score; FIB-4 = fibrosis-4 index; ELF = extended liver fibrosis panel; ProC3 = pro-collagen C3; ALT= alanine aminotransferase; TE = transient elastography; CAP = controlled attenuation parameter USS = ultrasound; HOMA-IR = homeostasis model of insulin resistance; HbA1c = haemoglobin A1c; TCA = tricarboxylic acid cycle; ATP = adenosine triphosphate; PDFF = proton density fat fraction.
| Pathogenic Pathway | Biological Process | Precision Imaging Endpoints | Other Endpoints |
|---|---|---|---|
| Metabolic Inflexibility | Insulin Resistance | 13C MRS (↓ postprandial net hepatic glycogen synthesis) | Dual Step Euglycaemic Hyperinsulinaemic Clamp to assess hepatic and peripheral insulin sensitivity Oral glucose tolerance test Wet biomarkers: Adiponectin, HbA1c, HOMA-IR |
| Liver fat Quantity (%) | MRI-PDFF, 1H MRS | TE with CAP, USS | |
| Liver fat Quality | 1H MRS | ||
| Inflammation | Oxidative Stress | 13C MRS (glutathione flux) | |
| Impaired Energy Kinetics |
31P MRS (ATP flux) 13C MRS (TCA cycle flux and β-oxidation) |
||
| Steatohepatitis | Risk Prediction Tools: OxNASH, NASH resolution score Wet biomarkers: ALT |
||
| Collagen deposition | Fibrosis burden | Magnetic Resonance Elastography (MRE) | Wet biomarkers: ELF, ProC3 |
| 31P MRS (PME/PDE ratios) | Risk prediction tools: FIB-4, NFS |